2. INTRODUCTION:
● Gastrointestinal Hormones constitutes group of
Harmone secreted by Enteroendocrine Cells in
stomach, pancreas and small intestine that controls
various functions of digestive organs.
● Enteroendocrine cells are specialized cells of
the gastrointestinal tracts and pancreas with
endocrine function.
●They produce gastrointestinal hormones or simple
polypeptides in response to various stimuli.
3. Classification of Gastrointestinal Hormones.
The hormones are classified into following groups based upon
their chemical nature.
■ Gastrin family: Gastrin and Cholecystokinin.
■ Secretin family: Secretin, Vasoactive intestinal
peptide(VIP), Gastric inhibitory peptide (GIP), Glucagon.
■ Others: Somatostatin, Motilin, substance P, Ghrelin.
4. Gastrin
■ Gastrin is a peptide hormone that stimulates
secretion of gastric acid(HCl) by the parietal
cells of the stomach
■ Gastrin is a linear peptide hormone produced
by G cells of the duodenum and in the
Pyloric antrum of the stomach.
■ 3 biologically active forms:
“Big gastrin”= 34 amino acids
‘Little gastrin” = 17 amino acids
“Mini gastrin” = 14 amino acids
■ Gastrin hormone family members contain a
biologically
active C-terminal pentapeptide sequence
5.
6. ■ Gastrin binds to cholecystokinin B receptors to stimulate
the release of histamines in enterochromaffin-like cells.
■ Gastrin induces the insertion of K+/H+ ATPase pumps into
the apical membrane of parietal cells, which in turn
increases H+ release into the stomach cavity.
■ Deficiency of gastrin may increases the risk of GIP tract
infection and improper absorption of nutrients.
■ Hypogastrinemia causes Gastroesophageal reflux (acid
reflux)
■ Release is stimulated by the increased pH and
presence of partially digested proteins,
especially amino acids, in the stomach.
■ Release causes the contraction of oesophagal
sphincter and relaxation of Pyloric sphincter.
7. Cholecystokinin
■ Cholecystokinin, previously called pancreozymin, is
synthesized and secreted by enteroendocrine cells in
the duodenum, the first segment of the small
intestine.
■ Cholecystokinin (cck) is a peptide hormone of
the gastrointestinal system responsible for stimulating
the digestion of fat and protein.
■ Cholecystokinin is a polypeptide belongs to Gastrin
family with 33 amino acid sequence
8. Amino acid sequence of human Cholecystokin - 33 amino
acids.
■ Cholecystokinin is the major hormone responsible
for gallbladder contraction and pancreatic enzyme
secretion.
■ CCK plays important physiologic roles both as a
in the central nervous system and as a peptide
hormone in the gastrointestinal tract.
9. ■ CCK also synthesized and released by neurons of
enteric nerve system, and neurons in the brain
■The greatest stimulator of CCK release is the
presence of fatty acid or certain amino acids in
the chyme with less pH, entering the duodenum
■The release of CCK is inhibited by somatostatin and
pancreatic peptide. Trypsin, a protease released by
pancreatic acinar cells, hydrolyzes CCK-releasing
peptide.
■ Deficiency of Cholecystokin causes impaired
gallbladder contractility and autoimmune polyglandular
syndrome.
10. Secretin.
■ Secretin is a 27 amino acid polypeptide hormone
secreted by S cell located deeply in the mucosa
gland of duodenum and jejunum.
His-Ser-Asp-Gly-Thr-Phe-Thr-Ser-Glu-Leu-Ser-Arg-Leu-
Arg-Asp-Ser-Ala-Arg-Leu-Gln-Arg-Leu-Leu-Gln-Gly-Leu-
Val-NH2
Amino acid sequence of Secretin(27-amino acids)
■ Secretin stimulated by the low pH of chyme.
■ Secretin regulate the pH of duodenum by
inhibiting the secretion of of Gastric acid of the
stomach and stimulating the production of
bicarbonate from the ductal cells of the pancreas.
11. ■ It also stimulate bile production by the liver, which
emulsifies the dietary fats in the duodenum.
■ It causes the contraction of Pyloric sphincter
■ Secretin in stored in an inactive form called
Prosecretin which Is activated by Gastric acid.
■ Secretin release is inhibited by somatostatin which
reduce gastric acid secretion. As a result, if the pH in
the duodenum increases above 4.5, secretin cannot be
released.
■ Deficiency of Secretin causes peptic ulcers that
develop in the lining of the stomach, lower esophagus,
or small intestine, formed as a result of inflammation
caused by the bacteria Helicobacter pylori.
12. Gastric inhibitory peptide (GIP)
■ GIP is synthesized by K cells, which are found in
the mucosa of the duodenum and the jejunum of
the gastrointestinal tract.
■ GIP is a polypeptide hormone with a sequence of 42
amino acids and belongs to Secretin family.
Tyr-Ala-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser- Ile-Ala-
Met-Asp-Lys-Ile-His-Gln-Gln-Asp-Phe- Val-Asn-Trp-
Leu-Leu-Ala-Gln-Lys-ly-Lys-Lys-Asn-Asp-Trp-Lys-His-
Asn-Ile-Thr-Gln
Amino acid sequence of GIP (42 amino acids)
13. ■ Gastric inhibitory polypeptide (GIP) or gastroinhibitory
peptide, also known as the glucose-dependent
insulinotropic peptide, is an inhibiting hormone Which
belongs to Secretin family.
■ Stimulated by glucose and fat in duodenum, acid in
stomach and secretes insulin from pancreatic islet.
■ It inhibits the gastric acid secretion by directly inhibiting
the parietal cells or indirectly inhibit gastrin release from
antral G cells.
■GIP receptors are seven-transmembrane proteins found
on beta-cells in the pancreas.
■ GIP deficiency results in the uncontrolled and excessive
secretion of gastrin leads to ulceration in duodenum,
stomach and small intestine.
14. Vasoactive intestinal peptide
■ Vasoactive intestinal peptide, also known
as vasoactive intestinal polypeptide or VIP, is
a peptide hormone that is vasoactive in the intestine
and also facilitates the coronary vasodilation.
■ VIP is a polypeptide hormone with 28 amino acid
residues and belongs to Secretin family.
His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-
Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Ile-Leu-Asn
Amino acid sequence of VIP ( 28 amino acids )
■ VIP induces smooth muscle relaxation (lower
esophageal sphincter, stomach, gallbladder).
15. ■ VIP released in response to esophageal and
gastric distension, Vagal stimulation in duodenum
■ VIP stimulate secretion of water into pancreatic
juice and bile, and cause inhibition of gastric acid
secretion and absorption from the intestinal lumen.
■ It stimulates the pepsinogen secretion by chief
cells.
■Vasoactive intestinal peptide (VIP) inhibits gastric
acid secretion and stimulates pancreatic
electrolyte and water secretion.
16. Glucagon
■ Glucagon is a peptide hormone, produced by alpha
cells of the pancreas.
■ Glucagon is a 28 amino acid polypeptide belongs
to Secretin family.
NH2-His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-
Ser-Lys-Tyr-Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-
Phe-Val-Gln-Trp-Leu-Met-Asn-Thr-COOH
Amino acid sequence of glucagon (28 amino acids )
17. ■ Its effect is opposite to that of insulin which lowers
the extracellular glucose.
■ Glucagon is stimulated by the lower concentration
of insulin in bloodstream.
■ Glucagon causes the liver to convert the stored
glycogen into glucose.
■ Glucagon deficiency is one of the major causes of
hypoglycemia, which lowers the blood glucose
levels.
■ Deficiency of glucagon causes inadequate supply
of glucose in the brain and resulting impairment of
function.
18. Somatostatin
■ Somatostatin is a Growth hormone inhibiting
hormone(GH-IH)
■ Somatostatin is secreted by delta cells in
stomach, duodenum, pancreatic islet.
■ Somatostatin is released in response to acid in
stomach.
■ Somatostatin mainly inhibit the secretion of
gastrin and growth hormone.
■ It increases fluid absorption from intestine
19. ■ Somatostatin present in 2 forms,
1.somatostatin 14 : prominent in hypothalamus
2.somatostatin 28 :prominent in GI tract
Amino acid sequence of
somatostatin 14
somatostatin 28
20. ■ Suppresses the release of pancreatic hormones
■ Somatostatin acts directly on the acid-
producing parietal cell and indirectly decrease
stomach acid production by preventing the release of
other hormones,including gastrin, secretin and
histamine.
■ Decreases the absorption of glucose, amino acid and
triglyceride
■ Somatostatin Deficiency results in the uncontrolled
and excessive secretion of gastrin leads to ulceration
in duodenum, stomach and small intestine.
■ Deficiency may contribute to excessive secretion of
growth hormone leads to Hyperthyroidism.
21. Motilin
■ Motilin is secreted by enteroendocrine epithelial M
cells located in duodenum and jejuinum.
■ Motilin is a peptide hormone with 22 amino acids.
NH2-Phe-Val-Pro-Ile-Phe-Thr-Tyr-Gly-Glu-
Leu-Glu-Arg-Met-Gln-Glu-Lys-Glu-Arg-Asn-
Lys-Gly-Gln-COOH
Amino acid sequence of Motilin ( 22 amino acids ).
■ Motilin participates in controlling the pattern of
smooth muscle contraction in upper GI tract
22. ■ Alkaline pH in duodenum stimulates the release of motilin
■ Main function of Motilin is to increase the
gastrointestinal motility and stimulate the production of
pepsin.
■ Motilin participates in controlling the pattern of smooth
muscle contraction in upper GI tract.
■ Deficiency of Motilin
●lower gastrointestinal motility
● abnormal contraction of smooth muscle of intestine
which causes severe Constipation
●Gastroesophageal reflux
23. Substance P
■ Substance P is a peptide with a chain of 11 amino
acid residues.
Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-
Met
Amino acid sequence of substance P( 11 amino acids )
■ Substance P is an effective neurotransmitter
belongs to neuropeptide family Which is present in
brain and as well as in gut.
24. ■ Substance P involved contraction of intestinal
smooth muscles and regulates blood glucose levels.
■ Potential vasodilator which widens the blood
vessels and cause the release of nitric oxide
(gaseous hormone).
■ Stimulate secretion of histamine from master cell.
■ Deficiency in substance P may contribute to
● Alzheimer’s development.
● Type 1 diabetes.
25. Gherlin
■ Ghrelin is a peptide hormone With 28 amino acids
produced predominantly in the stomach.
Amino acid sequence of gherlin( 28 amino acids ) with a n-Octanoyl
attached to serine at 3rd position.
26. ■Gherlin is also called hunger hormone, which is
secreted when the stomach is empty.
■ Gherlin stimulates the secretion of growth
hormone from the pituitary gland.
■ Gherlin increases the gastric acid secretion
and gastrointestinal motility.
■ Increased levels of gherlin during fasting, Peak
level before meal and fall rapidly after meal.
■ Deficiency of gherlin causes poor energy
balance (energy homeostasis) in the body and
poor Growth hormone regulation.